Ectopeptidases pp 223-257 | Cite as

DPIV — Natural Substrates of Medical Importance

  • Ingrid de Meester
  • Christine Durinx
  • Paul Proost
  • Simon Scharpé
  • Anne-Marie Lambier


In a continuing attempt to unravel the in vivo function of this abundant but highly regulated enzyme, the hydrolysis of bioactive peptides by DPIV has been studied extensively (Mentlein 1999). This chapter focuses on recent data concerning a number of human naturally occurring peptides that are cleaved by DPIV in vitro and that may be substrates in vivo. A summary of the kinetic parameters of the processing by DPIV can be found at the end of this chapter.


Vasoactive Intestinal Peptide Pituitary Adenylate Cyclase Activate Polypeptide Gastric Inhibitory Polypeptide Dipeptidyl Peptidase Gastrin Release Peptide 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adrian, T.E., Savage, A.P., Sagor, G.R., Allen, J.M., Bacarese-Hamilton, A.J., Tatemoto, K., Polak, J.M., and Bloom, S.R., 1985, Effect of peptide YY on gastric, pancreatic, and biliary function in humans.Gastroenterology 89: 494–499.PubMedGoogle Scholar
  2. Ahrén, B., 2000, Autonomic regulation of islet hormone secretion-implications for health and disease.Diabetologia 43: 393–410.PubMedGoogle Scholar
  3. Aitman, T.J., Rafferty, B., Coy, D., Lynch, S.S., and Clayton, R.N., 1989, Bioactivity of growth hormone releasing hormone (1–29) analogues after SC injection in man.Peptides 10: 1–4PubMedGoogle Scholar
  4. Alford, F.P., Bloom S.R., and Nabarro, J.D., 1976, Glucagon metabolism in man, studies on the metabolic clearance rate and the plasma acute disappearance time of glucagon in normal and diabetic subjects.J. Clin. Endocrinol Metab.42: 830–838.PubMedGoogle Scholar
  5. Assicot, M., Gendrel, D., Carsin, H., Raymond, J., Guilbaud, J., and Bohuon, C., 1993, High serum procalcitonin concentrations in patients with sepsis and infection.Lancet 341: 515–518.PubMedGoogle Scholar
  6. Baggiolini, M., 1998, Chemokines and leukocyte traffic.Nature 392: 565–568.PubMedGoogle Scholar
  7. Baggiolini, M., 2001, Chemokines in pathology and medicine.J. Intern. Med.250: 91–104.PubMedGoogle Scholar
  8. Bailey, C.J., Wilkes, L.C., Conlon, J.M, Armstrong, P.H., and Buchanan, K.D., 1990, Effects of gastric inhibitory polypeptide, vasoactive intestinal polypeptide and peptide histidine isoleucine on the secretion of hormones by isolated mouse pancreatic islets.J. Endocrinol.125: 375–379.PubMedGoogle Scholar
  9. Balkan, B., Kwasnik, L., Miserendino, R., Hoist, J.J., and Li, X., 1999, Inhibition of dipeptidyl peptidase IV with NVP-DPP728 increases plasma GLP–1 (7–36 amide) concentrations and improves oral glucose tolerance in obese Zucker rats.Diabetologia 42: 1324–1331.PubMedGoogle Scholar
  10. Beck-Sickinger, A.G., Wieland, H.A., Wittneben, H., Willim, K.D., Rudolf, K., and Jung, G., 1994, Complete L-alanine scan of neuropeptide Y reveals ligands binding to Yl and Y2 receptors with distinguished conformations.Eur. J. Biochem.225: 947–958.PubMedGoogle Scholar
  11. Bird, A.P., Faltinek, J.R., and Shojaei, A.H., 2001, Transbuccal peptide delivery: stability and in vitro permeation studies on endomorphin-1.J. Control Release 73: 31–36.PubMedGoogle Scholar
  12. Bongers, J., Lambros, T., Ahmad, M., and Heimer, E.P., 1992, Kinetics of dipeptidyl peptidase IV proteolysis of growth hormone-releasing factor and analogs. Biochim. .Biophys. Acta 1122: 147–153.Google Scholar
  13. Bouras, M., Huneau, J.F., Luengo, C., Erlanson-Albertsson, C., and Tome, D., 1995, Metabolism of enterostatin in rat intestine, brain membranes, and serum: differential involvement of proline-specific peptidases.Peptides 16: 399–405.PubMedGoogle Scholar
  14. Boushey, R.P., Yusta, B., and Drucker, D.J., 2001, Glucagon-like peptide (GLP)-2 reduces chemotherapy-associated mortality and enhances cell survival in cells expressing a transfected GLP-2 receptor.Cancer Res.61: 687–693.PubMedGoogle Scholar
  15. Brenneman, D.E., Nicol, T., Warren, D., and Bowers, L.M., 1990, Vasoactive intestinal peptide: a neurotrophic releasing agent and an astroglial mitogen.J. Neurosci. Res.25: 386–394.PubMedGoogle Scholar
  16. Broome, M., Hokfelt, T., and Terenius, L., 1985, Peptide YY (PYY)-immunoreactive neurons in the lower brain stem and spinal cord of rat.ActaPhysiol. Scand.125: 349–352.Google Scholar
  17. Brown, J.C., Dahl, M., Kwauk, S., Mclntosh, C.H., Otte, S.C., and Pederson, R.A., 1981, Actions of GIP.Peptides 2: 241–245.PubMedGoogle Scholar
  18. Brown, J.C. and Dryburgh, J.R., 1971, A gastric inhibitory polypeptide. II. The complete amino acid sequence.Can. J. Biochem.49: 867–872.PubMedGoogle Scholar
  19. Brubaker, P.L., Crivici, A., Izzo, A., Ehrlich, P., Tsai, C.H., and Drucker, D.J., 1997, Circulating and tissue forms of the intestinal growth factor, glucagon-like peptide-2.Endocrinology 138: 4837–4843.PubMedGoogle Scholar
  20. Burcelin, R., Dolci, W., and Thorens, B., 1999, Long-lasting antidiabetic effect of a dipeptidyl peptidase IV-resistant analog of glucagon-like peptide-1.Metabolism 48: 252–258.PubMedGoogle Scholar
  21. Cervini, L.A., Donaldson, C.J., Koerber, S.C., Vale, W.W., and Rivier, J.E., 1998, Human growth hormone-releasing hormone hGHRH(l-29)-NH2: systematic structure-activity relationship studies.J. Med. Chem.41: 111–121.Google Scholar
  22. Chance, W.T., Zhang, X., Balasubramaniam, A., and Fischer, J.E., 1996, Preservation of intestine protein by peptide YY during total parenteral nutrition.Life Sci.58: 1785–1794.PubMedGoogle Scholar
  23. Cheeseman, C.I. and Tsang, R., 1996, The effect of GIP and glucagon-like peptides on intestinal basolateral membrane hexose transport.Am. J. Physiol.271: G477–G482.PubMedGoogle Scholar
  24. Christophe, J., Svoboda, M., Dehaye, J.P., Winand, J., Vandermeers-Pire, M.C., Vandermeers, A., Cauvin, A., Gourlet, P., and Robberecht, P., 1989, The VIP/PHIlsecretin/ helodermin/helospectin/GRF family: structure-function relationship of the natural peptides, their precursors and synthetic analogues as tested in vitro on receptors and adenylate cyclase in a panel of tissue membranes. In: Peptide hormones as pro-hormones: processing, biological activity, pharmacology. Martinez J., ed. Ellis Horwood, Chichester, p. 211–243.Google Scholar
  25. Chu, K.U., Higashide, S., Evers, B.M., Ishizuka, J., Townsend, CM., Jr., and Thompson, J.C., 1995, Bombesin stimulates mucosal growth in jejunal and ileal Thiry-Vella fistulas.Ann. Surg.221: 602–609.PubMedGoogle Scholar
  26. Clive, S., Jodrell, D., and Webb, D., 2001, Gastrin-releasing peptide is a potent vasodilator in humans.Clin. Pharmacol. Ther.69: 252–259.PubMedGoogle Scholar
  27. Conroy, D.M., St Pierre, S., and Sirois, P., 1995, Relaxant effects of pituitary adenylate cyclase activating polypeptide (PACAP) on epithelium-intact and -denuded guinea-pig trachea: a comparison with vasoactive intestinal peptide (VIP).Neuropeptides 29: 121–127.PubMedGoogle Scholar
  28. D’Alessio, D.A., Prigeon, R.L., and Ensinck, J.W., 1995, Enteral enhancement of glucose disposition by both insulin-dependent and insulin-independent processes. A physiological role of glucagon-like peptide I.Diabetes 44: 1433–1437.PubMedGoogle Scholar
  29. D’Alessio, D.A., Vogel, R., Prigeon, R., Laschansky, E., Koerker, D., Eng, J., and Ensinck, J.W., 1996, Elimination of the action of glucagon-like peptide 1 causes an impairment of glucose tolerance after nutrient ingestion by healthy baboons.J. Clin. Invest.97: 133–138.PubMedGoogle Scholar
  30. De Meester, I., Durinx, C., Bal, G., Proost, P., Struyf, S., Goossens, F., Augustyns, K., and Scharpé, S., 2000, Natural substrates of dipeptidyl peptidase IV.Adv. Exp. Med. Biol.471: 67–87.Google Scholar
  31. Deacon, C.F., Danielsen, P., Klarskov, L., Olesen, M., and Hoist, J.J., 2001, Dipeptidyl peptidase IV inhibition reduces the degradation and clearance of GIP and potentiates its insulinotropic and antihyperglycemic effects in anesthetized pigs.Diabetes 50: 1588–1597.PubMedGoogle Scholar
  32. Deacon, C.F., Hoist, J.J., and Carr, R.D., 1999, Glucagon-like peptide-1: a basis for new approaches to the management of diabetes.Drugs of today 35: 159–170.PubMedGoogle Scholar
  33. Deacon, C.F., Knudsen, L.B., Madsen, K., Wiberg, F.C., Jacobsen, O., and Hoist, J.J., 1998, Dipeptidyl peptidase IV resistant analogues of glucagon-like peptide-1 which have extended metabolic stability and improved biological activity.Diabetologia 41: 271–278.PubMedGoogle Scholar
  34. Deacon, C.F., Nauck, M.A., Meier, J., Hucking, K., and Hoist, J.J., 2000, Degradation of endogenous and exogenous gastric inhibitory polypeptide in healthy and in type 2 diabetic subjects as revealed using a new assay for the intact peptide.J. Clin. Endocrinol Metab.85: 3575–3581.PubMedGoogle Scholar
  35. Degen, L.P., Peng, F., Collet, A., Rossi, L., Ketterer, S., Serrano, Y., Larsen, F., Beglinger, C., and Hildebrand, P., 2001, Blockade of GRP receptors inhibits gastric emptying and gallbladder contraction but accelerates small intestinal transit.Gastroenterology 120: 361–368.PubMedGoogle Scholar
  36. Del Rio, M. and De la Fuente, M., 1994a, Chemoattractant capacity of bombesin, gastrinreleasing peptide and neuromedin C is mediated through PKC activation in murine peritoneal leukocytes.Regul. Pept.49: 185–193.PubMedGoogle Scholar
  37. Del Rio, M., Hernanz, A., and De la Fuente, M., 1994b, Bombesin, gastrin-releasing peptide, and neuromedin C modulate murine lymphocyte proliferation through adherent accessory cells and activate protein kinase C.Peptides 15: 15–22.PubMedGoogle Scholar
  38. Delgado, M., Abad, C., Martinez, C., Leceta, J., and Gomariz, R.P., 2001b, Vasoactive intestinal peptide prevents experimental arthritis by downregulating both autoimmune and inflammatory components of the disease.Nat. Med.7: 563–568.PubMedGoogle Scholar
  39. Delgado, M. and Ganea, D., 2001a, Cutting edge: is vasoactive intestinal peptide a type 2 cytokine?J. Immunol.166: 2907–2912.PubMedGoogle Scholar
  40. Delgado, M., Leceta, J., Gomariz, R.P., and Ganea, D., 1999a, Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide stimulate the induction of Th2 responses by up-regulating B7.2 expression.J. Immunol.163: 3629–3635.PubMedGoogle Scholar
  41. Delgado, M., Munoz-Elias, E.J., Martinez, C., Gomariz, R.P., and Ganea, D., 1999b, VIP and PACAP38 modulate cytokine and nitric oxide production in peritoneal macrophages and macrophage cell lines.Ann. NY Acad. Sci.897: 401–414.PubMedGoogle Scholar
  42. Delgado, M.B., Clark-Lewis, I., Loetscher, P., Langen, H., Thelen, M., Baggiolini, M., and Wolf, M., 2001, Rapid inactivation of stromal cell-derived factor-1 by cathepsin G associated with lymphocytes.Eur. J Immunol.31: 699–707.PubMedGoogle Scholar
  43. Deng, X., Guarita, D.R., Wood, P.G., Kriess, C., and Whitcomb, D.C., 2001, PYY potently inhibits pancreatic exocrine secretion mediated through CCK-secretin-stimulated pathways but not 2-DG-stimulated pathways in awake rats.Dig. Dis. Sci.46: 156–165.PubMedGoogle Scholar
  44. Dhanvantari, S., Seidah, N.G., and Brubaker, P.L., 1996, Role of prohormone convertases in the tissue-specific processing of proglucagon.Mol. Endocrinol.10: 342–355.PubMedGoogle Scholar
  45. Dickinson, T. and Fleetwood-Walker, S.M., 1999, VIP and PACAP: very important in pain?Trends Pharmacol. Sci.20: 324–329.PubMedGoogle Scholar
  46. Ding, W.G., Renstrom, E., Rorsman, P., Buschard, K., and Gromada, J., 1997, Glucagon-like peptide I and glucose-dependent insulinotropic polypeptide stimulate Ca2+-induced secretion in rat alpha-cells by a protein kinase A-mediated mechanism.Diabetes 46: 792–800.PubMedGoogle Scholar
  47. Doods, H., Gaida, W., Wieland, H.A., Dollinger, H., Schnorrenberg, G., Esser, F., Engel, W., Eberlein, W., and Rudolf, K., 1999, BIIE0246: a selective and high affinity neuropeptide Y Y(2) receptor antagonist.Eur. J. Pharmacol.384: R3–R5.PubMedGoogle Scholar
  48. Drucker, D.J., 2001, Minireview: the glucagon-like peptides.Endocrinology 142: 521–527.PubMedGoogle Scholar
  49. Drucker, D. J., Erlich, P., Asa, S.L., and Brubaker, P.L., 1996, Induction of intestinal epithelial proliferation by glucagon-like peptide 2.Proc. Natl. Acad. Sci. USA 93: 7911–7916.PubMedGoogle Scholar
  50. Drucker, D.J., Shi, Q., Crivici, A., Sumner-Smith, M., Tavares, W., Hill, M., DeForest, L., Cooper, S., and Brubaker, P.L., 1997, Regulation of the biological activity of glucagonlike peptide 2 in vivo by dipeptidyl peptidase IV.Nat.Biotechnol 15: 673–677.PubMedGoogle Scholar
  51. Dunphy, J.L., Justice, F.A., Taylor, R.G., and Fuller, P.J., 1999, mRNA levels of dipeptidyl peptidase IV decrease during intestinal adaptation.J. Surg. Res.87: 130–133.PubMedGoogle Scholar
  52. Dupre, J., Ross, S.A., Watson, D., and Brown, J.C., 1973, Stimulation of insulin secretion by gastric inhibitory polypeptide in man.J. Clin. Endocrinol Metab.37: 826–828.PubMedGoogle Scholar
  53. Ebert, R., Nauck, M., and Creutzfeldt, W., 1991, Effect of exogenous or endogenous gastric inhibitory polypeptide (GIP) on plasma triglyceride responses in rats.Horm. Metab. Res.23: 517–521.PubMedGoogle Scholar
  54. Eckel, R.H., Fujimoto, W.Y., and Brunzell, J.D., 1979, Gastric inhibitory polypeptide enhanced lipoprotein lipase activity in cultured preadipocytes.Diabetes 28: 1141–1142.PubMedGoogle Scholar
  55. Edwards, CM., Todd, J.F., Mahmoudi, M., Wang, Z., Wang, R.M., Ghatei, M.A., and Bloom, S.R., 1999, Glucagon-like peptide 1 has a physiological role in the control of postprandial glucose in humans: studies with the antagonist exendin 9–39.Diabetes 48: 86–93.PubMedGoogle Scholar
  56. Farber, J.M., 2001, MG. In: Cytokine reference - Volume 1: ligands, Oppenheim, J.J. and Feldmann, M., eds. Academic Press, London, p. 1111–1117.Google Scholar
  57. Fehmann, H.C. and Goke, B., 1995, Characterization of GIP(l-30) and GIP(l-42) as stimulators of proinsulin gene transcription.Peptides 16: 1149–1152.PubMedGoogle Scholar
  58. Ferris, H.A., Carroll, R.E., Lorimer, D.L., and Benya, R.V., 1997, Location and characterization of the human GRP receptor expressed by gastrointestinal epithelial cells.Peptides 18: 663–672.PubMedGoogle Scholar
  59. Fridolf, T., Bottcher, G., Sundler, F., and Ahrén, B., 1991, GLP-1 and GLP-l(7–36) amide: influences on basal and stimulated insulin and glucagon secretion in the mouse.Pancreas 6: 208–215.PubMedGoogle Scholar
  60. Frohman, L.A., Downs, T.R., Heimer, E.P., and Felix, A.M., 1989, Dipeptidylpeptidase IV and trypsin-like enzymatic degradation of human growth hormone-releasing hormone in plasma.J. Clin. Invest.83: 1533–1540.PubMedGoogle Scholar
  61. Frohman, L.A. and Jansson, J.O., 1986, Growth hormone-releasing hormone.Endocr. Rev.7: 223–253.PubMedGoogle Scholar
  62. Gallwitz, B., Ropeter, T., Morys-Wortmann, C., Mentlein, R., Siegel, E.G., and Schmidt, W.E., 2000, GLP-1-analogues resistant to degradation by dipeptidyl-peptidase IV in vitro.Regul. Pept.86: 103–111.PubMedGoogle Scholar
  63. Gefel, D., Hendrick, G.K., Mojsov, S., Habener, J., and Weir, G.C., 1990, Glucagon-like peptide-I analogs: effects on insulin secretion and adenosine 3’, 5’-monophosphate formation.Endocrinology 126: 2164–2168.PubMedGoogle Scholar
  64. Gerard, Y., Hober, D., Assicot, M., Alfandari, S., Ajana, F., Bourez, J.M., Chidiac, C., Mouton, Y., Bohuon, C., and Wattre, P., 1997, Procalcitonin as a marker of bacterial sepsis in patients infected with HIV-1.J. Infect.35: 41–46.PubMedGoogle Scholar
  65. Ghatei, M.A., Jung, R.T., Stevenson, J.C., Hillyard, C.J., Adrian, T.E., Lee, Y.C., Christofides, N.D., Sarson, D.L., Mashiter, K., Maclntyre, I., and Bloom, S.R., 1982, Bombesin: action on gut hormones and calcium in man.J. Clin. Endocrinol. Metab.54: 980–985.PubMedGoogle Scholar
  66. Ghersi, G., Chen, W., Lee, E.W., and Zukowska, Z., 2001, Critical role of dipeptidyl peptidase IV in neuropeptide Y-mediated endothelial cell migration in response to wounding.Peptides 22: 453–458.PubMedGoogle Scholar
  67. Goetzl, E.J., Voice, J.K., and Dorsam, G., 2001, VIP and PACAP. In : Cytokine reference - Volume 1: ligands, Oppenheim, J.J. and Feldmann, M., eds. Academic Press, London, p. 1397–1405.Google Scholar
  68. Gomez, G., Udupi, V., and Greeley, G.H., 1999, Peptide YY. in: Gastro-intestinal endocrinology, Greeley, G.H., ed., Humana Press, Totowa. p.551–576.Google Scholar
  69. Goumain, M., Voisin, T., Lorinet, A.M., Ducroc, R., Tsocas, A., Roze, C., Rouet-Benzineb, P., Herzog, H., Balasubramaniam, A., and Laburthe, M., 2001, The peptide YY-preferring receptor mediating inhibition of small intestinal secretion is a peripheral Y(2) receptor: pharmacological evidence and molecular cloning.Mol Pharmacol 60: 124–134.PubMedGoogle Scholar
  70. Grandt, D., Dahms, P., Schimiczek, M., Eysselein, V.E., Reeve, J.R., andMentlein, R., 1993, Proteolytic processing by dipeptidyl aminopeptidase IV generates receptor selectivity for peptide YY (PYY).Med. Klin.88: 143–145.Google Scholar
  71. Greeley, G.H., Jr., Partin, M., Spannagel, A., Dinh, T., Hill, F.L., Trowbridge, J., Salter, M., Chuo, H.F., and Thompson, J.C., 1986, Distribution of bombesin-like peptides in the alimentary canal of several vertebrate species.Regui Pept.16: 169–181.Google Scholar
  72. Gressens, P., Hill, J.M., Paindaveine, B., Gozes, I., Fridkin, M., and Brenneman, D.E., 1994, Severe microcephaly induced by blockade of vasoactive intestinal peptide function in the primitive neuroepithelium of the mouse.J. Clin. Invest.94: 2020–2027.PubMedGoogle Scholar
  73. Grider, J.R. and Foxx-Orenstein, A.E., 1999, Neuroendocrine regulation of intestinal peristalsis. In: Gastro-intestinal endocrinology, Greeley, G.H., ed., Humana Press, Totowa. p. 299–319.Google Scholar
  74. Grondin, G., Hooper, N.M., and LeBel, D., 1999, Specific localization of membrane dipeptidase and dipeptidyl peptidase IV in secretion granules of two different pancreatic islet cells.J. Histochem. Cytochem.47: 489–498.PubMedGoogle Scholar
  75. Gutniak, M.K., Juntti-Berggren, L., Hellstrom, P.M., Guenifi, A., Hoist, J.J., and Efendic, S., 1996, Glucagon-like peptide I enhances the insulinotropic effect of glibenclamide in NIDDM patients and in the perfused rat pancreas.Diabetes Care 19: 857–863.PubMedGoogle Scholar
  76. Gutzwiller, J.P., Drewe, J., Goke, B., Schmidt, H., Rohrer, B., Lareida, J., and Beglinger, C., 1999, Glucagon-like peptide-1 promotes satiety and reduces food intake in patients with diabetes mellitus type 2.Am. J. Physiol 276: R1541–R1544.PubMedGoogle Scholar
  77. Hartmann, B., Harr, M.B., Jeppesen, P.B., Wojdemann, M., Deacon, C.F., Mortensen, P.B., and Hoist, J.J., 2000a,In vivoand in vitro degradation of glucagon-like peptide-2 in humans.J. Clin. Endocrinol Metab. 85: 2884–2888.PubMedGoogle Scholar
  78. Hartmann, B., Thulesen, J., Kissow, H., Thulesen, S., Orskov, C., Ropke, C., Poulsen, S.S., and Hoist, J.J., 2000b, Dipeptidyl peptidase IV inhibition enhances the intestinotrophic effect of glucagon-like peptide-2 in rats and mice.Endocrinology 141: 4013–4020.PubMedGoogle Scholar
  79. Heimbrook, D.C., Boyer, M.E., Garsky, V.M., Balishin, N.L., Kiefer, D.M., Oliff, A., and Riemen, M.W., 1988, Minimal ligand analysis of gastrin releasing petide. Receptor binding and mitogenesis.J. Biol. Chem.263: 7016–7019.PubMedGoogle Scholar
  80. Henning, RJ. and Sawmiller, D.R., 2001, Vasoactive intestinal peptide: cardiovascular effects.Cardiovasc. Res.49: 27–37.PubMedGoogle Scholar
  81. Herrera, C., Morimoto, C., Blanco, J., Mallol, J., Arenzana, F., Lluis, C, and Franco, R., 2001, Comodulation of CXCR4 and CD26 in human lymphocytes.J. Biol. Chem.276: 19532–19539.PubMedGoogle Scholar
  82. Herrmann-Rinke, C., Voge, A., Hess, M., and Goke, B., 1995, Regulation of glucagon-like peptide-1 secretion from rat ileum by neurotransmitters and peptides.J. Endocrinol.147: 25–31.PubMedGoogle Scholar
  83. Heuser, M., Pfaar, O., Gralla, O., Grone, H.J., Nustede, R., and Post, S., 2000, Impact of gastrin-releasing peptide on intestinal microcirculation after ischemia-reperfusion in rats.Digestion 61: 172–180.PubMedGoogle Scholar
  84. Hinke, S.A., Pospisilik, J.A., Demuth, H.U., Mannhart, S., Kuhn-Wache, K., Hoffmann, T., Nishimura, E., Pederson, R.A., and Mclntosh, C.H., 2000, Dipeptidyl peptidase IV (DPIV/CD26) degradation of glucagon. Characterization of glucagon degradation products and DPIV-resistant analogs.J. Biol. Chem.275: 3827–3834.PubMedGoogle Scholar
  85. Hoist, J.J. and Deacon, C.F., 1998, Inhibition of the activity of dipeptidyl-peptidase IV as a treatment for type 2 diabetes.Diabetes 47: 1663–1670.Google Scholar
  86. Horstmann, O., Nustede, R., Schmidt, W., Stockmann, F., and Becker, H., 1999, On the role of gastrin-releasing peptide in meal-stimulated exocrine pancreatic secretion.Pancreas 19: 126–132.PubMedGoogle Scholar
  87. Hu, Y., Bloomquist, B.T., Cornfield, L.J., DeCarr, L.B., Flores-Riveros, J.R., Friedman, L., Jiang, P., Lewis-Higgins, L., Sadlowski, Y., Schaefer, J., Velazquez, N., and McCaleb, M.L., 1996, Identification of a novel hypothalamic neuropeptide Y receptor associated with feeding behavior.J. Biol. Chem.271: 26315–26319.PubMedGoogle Scholar
  88. Inui, A., 1999, Neuropeptide Y feeding receptors: are multiple subtypes involved?Trends Pharmacol.Sci.20: 43–46.PubMedGoogle Scholar
  89. Ito, T., Igarashi, H., Pradhan, T.K., Hou, W., Mantey, S.A., Taylor, J.E., Murphy, W.A., Coy, D.H., and Jensen, R.T., 2001, GI side-effects of a possible therapeutic GRF analogue in monkeys are likely due to VIP receptor agonist activity.Peptides 22: 1139–1151.PubMedGoogle Scholar
  90. Iwata, S., Yamaguchi, N., Munakata, Y., Daishima, H., Lee, J.F., Hosono, O., Schlossman, S.F., and Morimoto, C., 1999, CD26/dipeptidyl peptidase IV differentially regulates the chemotaxis of T cells and monocytes toward RANTES: possible mechanism for the switch from innate to acquired immune response.Int.Immunol.11: 417–426.PubMedGoogle Scholar
  91. Jamen, F., Persson, K., Bertrand, G., Rodriguez-Henche, N., Puech, R., Bockaert, J., Ahren, B., and Brabet, P., 2000, PAC1 receptor-deficient mice display impaired insulinotropic response to glucose and reduced glucose tolerance.J. Clin. Invest.105: 1307–1315.PubMedGoogle Scholar
  92. Jensen, R.T., Coy, D.H., Saeed, Z.A., Heinz-Erian, P., Mantey, S., and Gardner, J.D., 1988, Interaction of bombesin and related peptides with receptors on pancreatic acinar cells.Ann. NYAcad. Sci.547: 138–149.Google Scholar
  93. Jeppesen, P.B., Hartmann, B., Thulesen, J., Graff, J., Lohmann, J., Hansen, B.S., Tofteng, F., Poulsen, S.S., Madsen, J.L., Hoist, J.J., and Mortensen, P.B., 2001, Glucagon-like peptide 2 improves nutrient absorption and nutritional status in short-bowel patients with no colon.Gastroenterology 120: 806–815.PubMedGoogle Scholar
  94. Karlsson, S., Sundler, F., and Ahrén, B., 1998, Insulin secretion by gastrin-releasing peptide in mice: ganglionic versus direct islet effect.Am. J. Physiol.274: E124–E129.PubMedGoogle Scholar
  95. Karlsson, S., Sundler, F., and Ahrén, B., 2001, Direct cytoplasmic Ca(2+) responses to gastrin-releasing peptide in single beta cells. Biochem. Biophys. Res. Commun. 280: 610–614.PubMedGoogle Scholar
  96. Kastin, A.J., Banks, W.A., Hahn, K., and Zadina, J.E., 1994, Extreme stability of Tyr-MIF-1 in CSF.Neurosci. Lett.174: 26–28.PubMedGoogle Scholar
  97. Kato, T., Nagatsu, T., Fukasawa, K., Harada, M., Nagatsu, I., and Sakakibara, S., 1978, Successive cleavage of N-terminal Argl-Pro2 and Lys3-Pro4 from substance P but no release of Argl-Pro2 from bradykinin, by X-Pro dipeptidyl-aminopeptidase.Biochim. Biophys. Acta 525: 417–422PubMedGoogle Scholar
  98. Keire, D.A., Mannon, P., Kobayashi, M., Walsh, J.H., Solomon, T.E., and Reeve, J.R., Jr., 2000, Primary structures of PYY, (Pro(34))PYY, and PYY-(3–36) confer different conformations and receptor selectivity.Am. J. Physiol. Gastrointest. Liver Physiol.279: G126–G131.PubMedGoogle Scholar
  99. Kieffer, T.J., Mclntosh, C.H., and Pederson, R.A., 1995, Degradation of glucose-dependent insulinotropic polypeptide and truncated glucagon-like peptide 1 in vitro and in vivo by dipeptidyl peptidase IV.Endocrinology 136: 3585–3596.PubMedGoogle Scholar
  100. Kikuchi, M., Fukuyama, K., and Epstein, W.L., 1988, Soluble dipeptidyl peptidase IV from terminal differentiated rat epidermal cells: purification and its activity on synthetic and natural peptides.Arch. Biochem. Biophys.266: 369–376.PubMedGoogle Scholar
  101. Knudsen, L.B. and Pridal, L., 1996, Glucagon-like peptide-l-(9–36) amide is a major metabolite of glucagon-like peptide-l-(7–36) amide after in vivo administration to dogs, and it acts as an antagonist on the pancreatic receptor.Eur. J. Pharmacol 318: 429–435.PubMedGoogle Scholar
  102. Kühn-Wache, K., Manhardt, S., Rosche, F., Hoffmann, T., Pederson, A., and Demuth, H.-U., 1999, Extended substrate specificity of DPIV - role in processing bioactive peptides. In: Cellular peptidases in Immune Functions and Diseases, 2nd Symposium, Magdeburg Sept. 1999, Abstracts, p. 34.Google Scholar
  103. Krarup, T., Hoist, J.J., and Larsen, K.L., 1985, Responses and molecular heterogeneity of IRGIP after intraduodenal glucose and fat.Am. J. Physiol 249: E195–E200.PubMedGoogle Scholar
  104. L’Heureux, M.C. and Brubaker, P.L., 2001, Therapeutic potential of the intestinotropic hormone, glucagon-like peptide-2.Ann. Med.33: 229–235.PubMedGoogle Scholar
  105. Laburthe, M., Couvineau, A., and Voisin, T., 1999, Receptors for peptides of the VIP/PACAP and PYY/NPY/PP families. In: Gastro-intestinal endocrinology, Greeley, G.H., ed., Humana Press, Totowa. p 125–157.Google Scholar
  106. Lambeir, A.M., Durinx, C., Proost, P., Van Damme, J., Scharpé, S., and De Meester, I., 2001a, Kinetic study of the processing by dipeptidyl-peptidase IV/CD26 of neuropeptides involved in pancreatic insulin secretion.FEBS Lett, in pressGoogle Scholar
  107. Lambeir, A.M., Proost, P., Durinx, C., Bal, G., Senten, K., Augustyns, K., Scharpé, S., Van Damme, J., and De Meester, I., 2001b, Kinetic investigation of chemokine truncation by CD26/dipeptidyl peptidase IV reveals a striking selectivity within the chemokine family.J. Biol. Chem.276: 29839–29845.PubMedGoogle Scholar
  108. Levite, M., 1998, Neuropeptides, by direct interaction with T cells, induce cytokine secretion and break the commitment to a distinct T helper phenotype.Proc. Natl. Acad. Sci. USA 95: 12544–12549.PubMedGoogle Scholar
  109. Lin, M.C., Wright, D.E., Hruby, V.J., andRodbell, M., 1975, Structure-function relationships in glucagon: properties of highly purified des-His-1-, monoiodo-, and (des-Asn-28, Thr-29) (homoserine lactone-27)-glucagon.Biochemistry 14: 1559–1563.PubMedGoogle Scholar
  110. Lioudyno, M., Skoglosa, Y., Takei, N., and Lindholm, D., 1998, Pituitary adenylate cyclaseactivating polypeptide (PACAP) protects dorsal root ganglion neurons from death and induces calcitonin gene-related peptide (CGRP) immunoreactivity in vitro.J. Neurosci. Res.51: 243–256.PubMedGoogle Scholar
  111. Lovshin, J., Estall, J., Yusta, B., Brown, T.J., and Drucker, D.J., 2001, Glucagon-like peptide (GLP)-2 action in the murine central nervous system is enhanced by elimination of GLP-1 receptor signaling.J. Biol. Chem.276: 21489–21499.PubMedGoogle Scholar
  112. Lundberg, J.M. and Modin, A., 1995, Inhibition of sympathetic vasoconstriction in pigs in vivo by the neuropeptide Y-Yl receptor antagonist BIBP 3226.Br. J. Pharmacol.116: 2971–2982.PubMedGoogle Scholar
  113. Lundberg, J.M., Tatemoto, K., Terenius, L., Hellstrom, P.M., Mutt, V., Hokfelt, T., and Hamberger, B., 1982, Localization of peptide YY (PYY) in gastrointestinal endocrine cells and effects on intestinal blood flow and motility.Proc. Natl. Acad. Sci. USA 79: 4471– 4475.PubMedGoogle Scholar
  114. Lundell, I., Eriksson, H., Marklund, U., and Larhammar, D., 2001, Cloning and characterization of the guinea pig neuropeptide Y receptor Y5.Peptides 22: 357–363.PubMedGoogle Scholar
  115. Luster, A.D., 2001, IP-10. In : Cytokine reference - Volume 1: ligands, Oppenheim, J.J. and Feldmann, M., eds. Academic Press, London, p .1103–1109.Google Scholar
  116. Lü, F., Jin, T., and Drucker, D.J., 1996, Proglucagon gene expression is induced by gastrinreleasing peptide in a mouse enteroendocrine cell line.Endocrinology 137: 3710–3716.PubMedGoogle Scholar
  117. Mackay, C.R., 2001a, Chemokines: immunology’s high impact factors.Nat.Immunol.2: 95–101.PubMedGoogle Scholar
  118. Mackay, C.R., 2001b, SDF-1. In: Cytokine reference - Volume 1: ligands, Oppenheim, J.J. and Feldmann, M., eds. Academic Press, London, p 1119–1123.Google Scholar
  119. Mannon, P.J.and Mele, J.M., 2000, Peptide YY Yl receptor activates mitogen-activated protein kinase and proliferation in gut epithelial cells via the epidermal growth factor receptor.Biochem. J.350 Pt 3: 655–661.PubMedGoogle Scholar
  120. Marguet, D., Baggio, L., Kobayashi, T., Bernard, A.M., Pierres, M., Nielsen, P.F., Ribel, U., Watanabe, T., Drucker, D.J., and Wagtmann, N., 2000, Enhanced insulin secretion and improved glucose tolerance in mice lacking CD26.Proc. Natl. Acad. Sci. USA 97: 6874–6879.PubMedGoogle Scholar
  121. McCaughan, G.W., Gorrell, M.D., Bishop, G.A., Abbott, C.A., Shackel, N.A., McGuinness, P.H., Levy, M.T., Sharland, A.F., Bowen, D.G., Yu, D., Slaitini, L., Church, W.B., and Napoli, J., 2000, Molecular pathogenesis of liver disease: an approach to hepatic inflammation, cirrhosis and liver transplant tolerance.Immunol.Rev.174: 172–191.PubMedGoogle Scholar
  122. McDonald, T.J., Jomvall, H., Nilsson, G., Vagne, M., Ghatei, M., Bloom, S.R., and Mutt, V., 1979, Characterization of a gastrin releasing peptide from porcine non-antral gastric tissue.Biochem. Biophys. Res. Commun.90: 227–233.Google Scholar
  123. Medeiros, M.D. and Turner, A.J., 1994, Processing and metabolism of peptide-YY: pivotal roles of dipeptidylpeptidase-IV, aminopeptidase-P, and endopeptidase-24.11.Endocrinology 134: 2088–2094.PubMedGoogle Scholar
  124. Medina, S., Del Rio, M., Manuel Victor, V., Hernanz, A., and De la Fuente, M., 1998, Changes with ageing in the modulation of murine lymphocyte chemotaxis by CCK-8S, GRP and NPY.Mech. Ageing Dev.102: 249–261.PubMedGoogle Scholar
  125. Mentlein, R., 1999, Dipeptidyl-peptidase IV (CD26) - role in the inactivation of regulatory peptides.Regul. Pept.85: 9–24.PubMedGoogle Scholar
  126. Mentlein, R., Dahms, P., Grandt, D., and Kruger, R., 1993b, Proteolytic processing of neuropeptide Y and peptide YY by dipeptidyl peptidase IV.Regul. Pept.49: 133–144.PubMedGoogle Scholar
  127. Mentlein, R., Gallwitz, B., and Schmidt, W.E., 1993a, Dipeptidyl-peptidase IV hydrolyses gastric inhibitory polypeptide, glucagon-like peptide-l(7–36)amide, peptide histidine methionine and is responsible for their degradation in human serum.Eur. J. Biochem.214: 829–835.PubMedGoogle Scholar
  128. Mentlein, R. and Heymann, E., 1982, Dipeptidyl peptidase IV inhibits the polymerization of fibrin monomers.Arch. Biochem. Biophys.217: 748–750.PubMedGoogle Scholar
  129. Merali, Z., Mclntosh, J., and Anisman, H., 1999, Role of bombesin-related peptides in the control of food intake.Neuropeptides 33: 376–386.PubMedGoogle Scholar
  130. Miyawaki, K., Yamada, Y., Yano, H., Niwa, H., Ban, N., Ihara, Y., Kubota, A., Fujimoto, S., Kajikawa, M., Kuroe, A., Tsuda, K., Hashimoto, H., Yamashita, T., Jomori, T., Tashiro, F., Miyazaki, J., and Seino, Y., 1999, Glucose intolerance caused by a defect in the enteroinsular axis: a study in gastric inhibitory polypeptide receptor knockout mice.Proc. Natl. Acad. Sci. USA 96: 14843–14847.PubMedGoogle Scholar
  131. Moghimzadeh, E., Ekman, R., Hakanson, R., Yanaihara, N., and Sundler, F., 1983, Neuronal gastrin-releasing peptide in the mammalian gut and pancreas.Neuroscience 10: 553–563.PubMedGoogle Scholar
  132. Morgan, L.M., 1998, The role of gastrointestinal hormones in carbohydrate and lipid metabolism and homeostasis: effects of gastric inhibitory polypeptide and glucagon-like peptide-1.Biochem.Soc.Trans.26: 216–222.PubMedGoogle Scholar
  133. Nauck, M.A., Kleine, N., Orskov, C., Hoist, J.J., Willms, B., and Creutzfeldt, W., 1993, Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7–36 amide) in type 2 (non-insulin-dependent) diabetic patients.Diabetologia 36: 741–744.PubMedGoogle Scholar
  134. Nauck, M.A., Niedereichholz, U., Ettler, R., Hoist, J. J., Orskov, C, Ritzel, R., and Schmiegel,W.H., 1997, Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans.Am. J. Physiol.273: E981–E988.PubMedGoogle Scholar
  135. Nauck, M.A., Sauerwald, A., Ritzel, R., Hoist, J.J., and Schmiegel, W., 1998, Influence of glucagon-like peptide 1 on fasting glycemia in type 2 diabetic patients treated with insulin after sulfonylurea secondary failure.Diabetes Care 21: 1925–1931.PubMedGoogle Scholar
  136. Nausch, I. and Heymann, E., 1985, Substance P in human plasma is degraded by dipeptidyl peptidase IV, not by cholinesterase.J.Neurochem.44: 1354–1357.PubMedGoogle Scholar
  137. Nausch, I., Mentlein, R., and Heymann, E., 1990, The degradation of bioactive peptides and proteins by dipeptidyl peptidase IV from human placenta.Biol. Chem. Hoppe-Seyler 371:1113–1118.PubMedGoogle Scholar
  138. Nicole, P., Lins, L., Rouyer-Fessard, C, Drouot, C, Fulcrand, P., Thomas, A., Couvineau, A.,Martinez, J., Brasseur, R., and Laburthe, M., 2000, Identification of key residues for interaction of vasoactive intestinal peptide with human VPAC1 and VPAC2 receptors and development of a highly selective VPAC1 receptor agonist. Alanine scanning and molecular modeling of the peptide.J. Biol. Chem.275: 24003–24012.PubMedGoogle Scholar
  139. OHarte, F.P., Gray, A.M., and Flatt, P.R., 1998, Gastric inhibitory polypeptide and effects of glycation on glucose transport and metabolism in isolated mouse abdominal muscle.J.Endocrinol.156: 237–243.PubMedGoogle Scholar
  140. OHiarte, F.P., Mooney, M.H., Kelly, CM., and Flatt, P.R., 2000a, Improved glycaemic control in obese diabetic ob/ob mice using N-terminally modified gastric inhibitory polypeptide.J. Endocrinol.165: 639–648.Google Scholar
  141. O’Harte, F.P., Mooney, M.H., Kelly, CM., McKillop, A.M., and Flatt, P.R., 2001,Degradation and glycemic effects of His(7)-glucitol glucagon-like peptide-l(7–36)amide in obese diabetic ob/ob mice.Regul. Pept.96: 95–104.PubMedGoogle Scholar
  142. O’Harte, F.P., Mooney, M.H., Lawlor, A., and Flatt, P.R., 2000b, N-terminally modified glucagon-like peptide-1(7–36) amide exhibits resistance to enzymatic degradation while maintaining its antihyperglycaemic activityin vivo.Biochim. Biophys. Acta 1474: 13–22.PubMedGoogle Scholar
  143. Ohtsuki, T., Hosono, O., Kobayashi, H., Munakata, Y., Souta, A., Shioda, T., and Morimoto,C., 1998, Negative regulation of the anti-human immunodeficiency virus and chemotactic activity of human stromal cell-derived factor 1 alpha by CD26/dipeptidyl peptidase IV.FEBS Lett.431:236–240.PubMedGoogle Scholar
  144. Oravecz, T., Pall, M., Roderiquez, G., Gorrell, M.D., Ditto, M., Nguyen, N.Y., Boykins, R.,Unsworth, E., and Norcross, M.A., 1997, Regulation of the receptor specificity and function of the chemokine RANTES (regulated on activation, normal T cell expressed and secreted) by dipeptidyl peptidase IV (CD26)-mediated cleavage.J. Exp. Med.186: 1865–1872.PubMedGoogle Scholar
  145. Pappas, T.N., Debas, H.T., Goto, Y., and Taylor, I.L., 1985, Peptide YY inhibits mealstimulated pancreatic and gastric secretion.Am. J. Physiol.248: G118–G123.PubMedGoogle Scholar
  146. Park, S.K. and O’Dorisio, M.S., 1999, Neuroendocrine immune axis in the intestine. In:Gastro-intestinal endocrinology, Greeley, G.H., ed., Humana Press, Totowa. p. 265–297.Google Scholar
  147. Pauly, R.P., Demuth, H.U., Rosche, F., Schmidt, J., White, H.A., Lynn, F., Mclntosh, C.H.,and Pederson, R.A., 1999, Improved glucose tolerance in rats treated with the dipeptidyl peptidase IV (CD26) inhibitor Ile-thiazolidide.Metabolism 48: 385–389.PubMedGoogle Scholar
  148. Pauly, R.P., Rosche, F., Wermann, M., Mclntosh, C.H., Pederson, R.A., and Demuth, H.U.,1996, Investigation of glucose-dependent insulinotropic polypeptide-(l-42) and glucagonlike peptide-1 -(7–36) degradation in vitro by dipeptidyl peptidase IV using matrix-assisted laser desorption/ionization-time of flight mass spectrometry. A novel kinetic approach.J.Biol.Chem.271: 23222–23229.PubMedGoogle Scholar
  149. Pederson,R.A. and Brown, J.C., 1978, Interaction of gastric inhibitory polypeptide, glucose,and arginine on insulin and glucagon secretion from the perfused rat pancreas.Endocrinology 103: 610–615.PubMedGoogle Scholar
  150. Pederson, R.A., White, H.A., Schlenzig, D., Pauly, R.P., Mclntosh, C.H., and Demuth, H.U.,1998, Improved glucose tolerance in Zucker fatty rats by oral administration of the dipeptidyl peptidase IV inhibitor isoleucine thiazolidide.Diabetes 47: 1253–1258.PubMedGoogle Scholar
  151. Persson, K., Gingerich, R.L., Nayak, S., Wada, K., Wada, E., and Ahrén, B., 2000, Reduced GLP-1 and insulin responses and glucose intolerance after gastric glucose in GRP receptor-deleted mice.Am. J. Physiol. Endocrinol. Metab.279: E956–E962.PubMedGoogle Scholar
  152. Pospisilik, J.A., Hinke, S.A., Pederson, R.A., Hoffmann, T., Rosche, F., Schlenzig, D., Glund,K., Heiser, U., Mclntosh, C.H., and Demuth, H., 2001, Metabolism of glucagon by dipeptidyl peptidase IV (CD26).Regui Pept 96: 133–141.Google Scholar
  153. Pozo, D., Delgado, M., Martinez, M., Guerrero, J.M., Leceta, J., Gomariz, R.P., and Calvo,J.R., 2000, Immunobiology of vasoactive intestinal peptide (VIP). Immunol.Today 21: 7–11Google Scholar
  154. Prakash, A. and Goa, K.L., 1999, Sermorelin - A review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency.Biodrugs 12: 139–157.PubMedGoogle Scholar
  155. Proost, P., De Meester, I., Schols, D., Struyf, S., Lambeir, A.M., Wuyts, A., Opdenakker, G.,De Clercq, E., Scharpé, S., and Van Damme, J., 1998a, Amino-terminal truncation of chemokines by CD26/dipeptidyl-peptidase IV. Conversion of RANTES into a potent inhibitor of monocyte chemotaxis and HIV-1-infection.J. Biol. Chem.273: 7222–7227.PubMedGoogle Scholar
  156. Proost, P., Menten, P., Struyf, S., Schutyser, E., De Meester, I., and Van Damme, J., 2000,Cleavage by CD26/dipeptidyl peptidase IV converts the chemokine LD78beta into a most efficient monocyte attractant and CCR1 agonist.Blood 96: 1674–1680.PubMedGoogle Scholar
  157. Proost, P., Schutyser, E., Menten, P., Struyf, S., Wuyts, A., Opdenakker, G., Detheux, M.Parmentier, M., Durinx, C., Lambeir, A.M., Neyts, J., Liekens, S., Maudgal, P.C., Billiau,A., and Van Damme, J., 2001, Aminoterminal truncation of CXCR3 agonists impairs receptor signaling and lymphocyte chemotaxis, whilst preserving anti-angiogenic properties.Blood 98: in pressGoogle Scholar
  158. Proost, P., Struyf, S., Schols, D., Durinx, C., Wuyts, A., Lenaerts, J.P., De Clercq, E., De Meester, I., and Van Damme, J., 1998b, Processing by CD26/dipeptidyl-peptidase IV reduces the chemotactic and anti-HTV-l activity of stromal-cell-derived factor-1 alpha.FEBSLett.432: 73–76.Google Scholar
  159. Proost, P., Struyf, S., Schols, D., Opdenakker, G., Sozzani, S., Allavena, P., Mantovani, A.,Augustyns, K., Bal, G., Haemers, A., Lambeir, A.M., Scharpé, S., Van Damme, J., and De Meester, I., 1999, Truncation of macrophage-derived chemokine by CD26/dipeptidyl-peptidase IV beyond its predicted cleavage site affects chemotactic activity and CC chemokine receptor 4 interaction.J. Biol. Chem.274: 3988–3993.PubMedGoogle Scholar
  160. Ritzel, U., Leonhardt, U., Ottleben, M., Ruhmann, A., Eckart, K., Spiess, J., and Ramadori,G., 1998, A synthetic glucagon-like peptide-1 analog with improved plasma stability.J.Endocrinol.159: 93–102.PubMedGoogle Scholar
  161. Robberecht, P., Gourlet, P., de Neef, P., Woussen-Colle, M.C., Vandermeers-Piret, M.C.,Vandermeers, A., and Christophe, J., 1992, Structural requirements for the occupancy of pituitary adenylate-cyclase-activating-peptide (PACAP) receptors and adenylate cyclase activation in human neuroblastoma NB-OK-1 cell membranes. Discovery of PACAP(6–38) as a potent antagonist.Eur. J. Biochem.207: 239–246.PubMedGoogle Scholar
  162. Roberge, J.N., Gronau, K.A., and Brubaker, P.L., 1996, Gastrin-releasing peptide is a novel mediator of proximal nutrient-induced proglucagon-derived peptide secretion from the distal gut.Endocrinology 137: 2383–2388.PubMedGoogle Scholar
  163. Rocca, A.S. and Brubaker, P.L., 1999, Role of the vagus nerve in mediating proximal nutrient-induced glucagon-like peptide-1 secretion.Endocrinology 140: 1687–1694.PubMedGoogle Scholar
  164. Ronai, A.Z., Timar, J., Mako, E., Erdo, F., Gyarmati, Z., Toth, G., Orosz, G., Furst, S., and Szekely, J.I., 1999, Diprotin A, an inhibitor of dipeptidyl aminopeptidase IV(EC produces naloxone-reversible analgesia in rats.Life Sci.64: 145–152.PubMedGoogle Scholar
  165. Rose, M.T., Itoh, F., and Takahashi, Y., 1998, Effect of glucose-dependent insulinotropic polypeptide on whole-body glucose utilization in sheep.Exp. Physiol 83: 783–792.PubMedGoogle Scholar
  166. Sandhu, H., Wiesenthal, S.R., MacDonald, P.E., McCall, R.H., Tchipashvili, V., Rashid, S., Satkunarajah, M., Irwin, D.M., Shi, Z.Q., Brubaker, P.L., Wheeler, M.B., Vranic, M., Efendic, S., and Giacca, A., 1999, Glucagon-like peptide 1 increases insulin sensitivity in depancreatized dogs.Diabetes 48: 1045–1053.PubMedGoogle Scholar
  167. Schols, D., Proost, P., Struyf, S., Wuyts, A., De Meester, I., Scharpé, S., Van Damme, J., and De Clercq, E., 1998, CD26-processed RANTES(3–68), but not intact RANTES, has potent anti-HTV-1 activity.Antiviral Res.39: 175–187.PubMedGoogle Scholar
  168. Service, F.J., Heiling, V.J., Go, V.L., and Rizza, R.A., 1990, Lack of effect of gastric inhibitory polypeptide on hepatic and extrahepatic insulin action.J. Clin. Endocrinol. Metab.70: 1398–1402.PubMedGoogle Scholar
  169. Shane, R., Wilk, S., and Bodnar, R.J., 1999, Modulation of endomorphin-2-induced analgesia by dipeptidyl peptidase IV.Brain Res.815: 278–286.PubMedGoogle Scholar
  170. Sherwood, N.M., Krueckl, S.L., and McRory, J.E., 2000, The origin and function of the pituitary adenylate cyclase-activating polypeptide (PACAP)lglucagon superfamily.Endocr.Rev.21: 619–670.PubMedGoogle Scholar
  171. Shioda, T., Kato, H., Ohnishi, Y., Tashiro, K., Dcegawa, M., Nakayama, E.E., Hu, H., Kato, A., Sakai, Y., Liu, H., Honjo, T., Nomoto, A., Iwamoto, A., Morimoto, C., and Nagai, Y., 1998, Anti-HIV-1 and chemotactic activities of human stromal cell-derived factor 1 alpha (SDF-1 alpha) and SDF-lbeta are abolished by CD26/dipeptidyl peptidase IV-mediated cleavage.Proc. Natl. Acad. Sci. USA 95: 6331–6336.PubMedGoogle Scholar
  172. Siegel, E.G., Gallwitz, B., Scharf, G., Mentlein, R., Morys-Wortmann, C., Folsch, U.R., Schrezenmeir, J., Drescher, K., and Schmidt, W.E., 1999, Biological activity of GLP-1-analogues with N-terminal modifications.Regul.Pept.79: 93–102.PubMedGoogle Scholar
  173. Snider, R.H., Jr., Nylen, E.S., and Becker, K.L., 1997, Procalcitonin and its component peptides in systemic inflammation: immunochemical characterization.J. Investig. Med.45: 552–560.PubMedGoogle Scholar
  174. Soil, R.M., Dinger, M.C., Lundell, I., Larhammer, D., and Beck-Sickinger, A.G., 2001, Novel analogues of neuropeptide Y with a preference for the Yl-receptor.Eur. J. Biochem.268: 2828–2837.Google Scholar
  175. Starich, G.H., Bar, R.S., and Mazzaferri, E.L., 1985, GIP increases insulin receptor affinity and cellular sensitivity in adipocytes.Am. J. PhysioL 249: E603–E607.PubMedGoogle Scholar
  176. Struyf, S., De Meester, I., Scharpé, S., Lenaerts, J.P., Menten, P., Wang, J.M., Proost, P., and Van Damme, J., 1998a, Natural truncation of RANTES abolishes signaling through the CC chemokine receptors CCR1 and CCR3, impairs its chemotactic potency and generates a CC chemokine inhibitor.Eur. J. Immunol.28: 1262–1271.PubMedGoogle Scholar
  177. Struyf, S., Menten, P., Lenaerts, J.P., Put, W., D’Haese, A., De Clercq, E., Schols, D., Proost, P., and Van Damme, J., 2001, Diverging binding capacities of natural LD78beta isoforms of macrophage inflammatory protein-1 alpha to the CC chemokine receptors 1, 3 and 5 affect their anti-HIV-1 activity and chemotactic potencies for neutrophils and eosinophils.Eur. J. Immunol.31: 2170–2178.PubMedGoogle Scholar
  178. Struyf, S., Proost, P., Schols, D., De Clercq, E., Opdenakker, G., Lenaerts, J.P., Detheux, M., Parmentier, M., De Meester, I., Scharpé, S., and Van Damme, J., 1999, CD26/dipeptidyl-peptidase IV down-regulates the eosinophil chemotactic potency, but not the anti-HTV activity of human eotaxin by affecting its interaction with CC chemokine receptor 3.J. Immunol.162: 4903–4909.PubMedGoogle Scholar
  179. Struyf, S., Proost, P., Sozzani, S., Mantovani, A., Wuyts, A., De Clercq, E., Schols, D., and Van Damme, J., 1998b, Enhanced anti-HTV-l activity and altered chemotactic potency of NH2- terminally processed macrophage-derived chemokine (MDC) imply an additional MDC receptor.J. Immunol.161: 2672–2675.PubMedGoogle Scholar
  180. Tache, Y., Garrick, T., and Raybould, H., 1990, Central nervous system action of peptides to influence gastrointestinal motor function.Gastroenterology 98: 517–528.PubMedGoogle Scholar
  181. Tatemoto, K., 1982, Isolation and characterization of peptide YY (PYY), a candidate gut hormone that inhibits pancreatic exocrine secretion.Proc. Natl. Acad. Sci. USA 79: 2514–2518.PubMedGoogle Scholar
  182. Tavares, W., Drucker, D.J., and Brubaker, P.L., 2000, Enzymatic- and renal-dependent catabolism of the intestinotropic hormone glucagon-like peptide-2 in rats.Am. J. Physiol. Endocrinol. Metab.278: E134–E139.PubMedGoogle Scholar
  183. Thulesen, J., Hartmann, B., Nielsen, C., Hoist, J.J., and Poulsen, S.S., 1999, Diabetic intestinal growth adaptation and glucagon-like peptide 2 in the rat: effects of dietary fibre.Gut 45: 672–678.PubMedGoogle Scholar
  184. Tiruppathi, C., Miyamoto, Y., Ganapathy, V., and Leibach, F.H., 1993, Genetic evidence for role of DPP IV in intestinal hydrolysis and assimilation of prolyl peptides.Am. J. Physiol.265: G81–G89.PubMedGoogle Scholar
  185. Toft-Nielsen, M.B., Damholt, M.B., Madsbad, S., Hilsted, L.M., Hughes, T.E., Michelsen, B.K., and Hoist, J.J., 2001, Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients.J. Clin. Endocrinol. Metab.86: 3717–3723.PubMedGoogle Scholar
  186. Tourrel, C, Bailbe, D., Meile, M.J., Kergoat, M., and Portha, B., 2001, Glucagon-like peptide-1 and exendin-4 stimulate beta-cell neogenesis in streptozotocin-treated newborn rats resulting in persistently improved glucose homeostasis at adult age.Diabetes 50: 1562–1570.PubMedGoogle Scholar
  187. Tsai, C.H., Hill, M., Asa, S.L., Brubaker, P.L., and Drucker, D.J., 1997, Intestinal growthpromoting properties of glucagon-like peptide-2 in mice.Am. J. Physiol.273: E77–E84.PubMedGoogle Scholar
  188. Upp, J.R., Jr., Poston, G.J., MacLellan, D.G., Townsend, CM., Jr., Barranco, S.C., and Thompson, J.C., 1988, Mechanisms of the trophic actions of bombesin on the pancreas.Pancreas 3: 193–198.PubMedGoogle Scholar
  189. Usdin, T.B., Mezey, E., Button, D.C., Brownstein, M.J., and Bonner, T.I., 1993, Gastric inhibitory polypeptide receptor, a member of the secretin-vasoactive intestinal peptide receptor family, is widely distributed in peripheral organs and the brain.Endocrinology 133: 2861–2870.PubMedGoogle Scholar
  190. Van Coillie, E., Proost, P., Van Aelst, I., Struyf, S., Polfliet, M., De Meester, I., Harvey, D. J., Van Damme, J., and Opdenakker, G., 1998, Functional comparison of two human monocyte chemotactic protein-2 isoforms, role of the ammo-terminal pyroglutamic acid and processing by CD26/dipeptidyl peptidase IV.Biochemistry 37: 12672–12680.PubMedGoogle Scholar
  191. Vilsboll, T., Krarup, T., Deacon, C.F., Madsbad, S., and Hoist, J.J., 2001, Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients.Diabetes 50: 609–613.PubMedGoogle Scholar
  192. Wang, Z., Wang, R.M., Owji, A.A., Smith, D.M., Ghatei, M.A., and Bloom, S.R., 1995, Glucagon-like peptide-1 is a physiological incretin in rat.J. Clin. Invest.95: 417–421.PubMedGoogle Scholar
  193. Ward, S.G., Bacon, K., and Westwick, J., 1998, Chemokines and T lymphocytes: more than an attraction.Immunity 9: 1–11.PubMedGoogle Scholar
  194. Whitley, J.C., Giraud, A.S., Mahoney, A.O., Clarke, I.J., and Shulkes, A., 2000, Tissuespecific regulation of gastrin-releasing peptide synthesis, storage and secretion by oestrogen and progesterone.J. Endocrinol.166: 649–658.PubMedGoogle Scholar
  195. Wojdemann, M, Wettergren, A., Hartmann, B., Hilsted, L., and Hoist, J.J., 1999, Inhibition of sham feeding-stimulated human gastric acid secretion by glucagon-like peptide-2.J. Clin. Endocrinol Metab.84: 2513–2517.PubMedGoogle Scholar
  196. Wolf, R., Rosche, F., Hoffmann, T., and Demuth, H.U., 2001, hnmunoprecipitation and liquid chromatographic-mass spectrometric determination of the peptide glucose-dependent insulinotropic polypeptides GEP1–42 and GIP3–42 from human plasma samples. New sensitive method to analyze physiological concentrations of peptide hormones.J. Chromatogr.A 926: 21–27.PubMedGoogle Scholar
  197. Wrenger, S., Kähne, T., Bohuon, C., Weglohner, W., Ansorge, S., and Reinhold, D., 2000, Ammo-terminal truncation of procalcitonin, a marker for systemic bacterial infections, by dipeptidyl peptidase IV (DP IV).FEBSLett.466: 155–159.Google Scholar
  198. Xiao, D., Wang, J., Hampton, L.L., and Weber, H.C., 2001, The human gastrin-releasing peptide receptor gene structure, its tissue expression and promoter.Gene 264: 95–103.PubMedGoogle Scholar
  199. Xiao, Q., Boushey, R.P., Cino, M, Drucker, D.J., and Brubaker, P.L., 2000, Circulating levels of glucagon-like peptide-2 in human subjects with inflammatory bowel disease.Am. J. Physiol Regul. Integr. Comp. Physiol 278: R1057–R1063.PubMedGoogle Scholar
  200. Xiao, Q., Boushey, R.P., Drucker, D.J., and Brubaker, P.L., 1999, Secretion of the intestinotropic hormone glucagon-like peptide 2 is differentially regulated by nutrients in humans.Gastroenterology 117: 99–105.PubMedGoogle Scholar
  201. Yip, R.G. and Wolfe, M.M., 2000, GIP biology and fat metabolism.Life Sci.66: 91–103.PubMedGoogle Scholar
  202. Zlotnik, A., Morales, J., and Hedrick, J.A., 1999, Recent advances in chemokines and chemokine receptors.Crit Rev. Immunol.19: 1–47.PubMedGoogle Scholar
  203. Zukowska-Grojec, Z., 1997, Neuropeptide Y: implications in vascular remodeling and novel therapeutics.Drug News & Perspectives 10: 587–595.Google Scholar
  204. Zukowska-Grojec, Z., 1998, Neuropeptide Y: an adrenergic cotransmitter, vasoconstrictor, and a nerve-derived vascular growth factor.Adv. Pharmacol.42: 125–128.PubMedGoogle Scholar
  205. Zukowska-Grojec, Z., Dayao, E.K., Karwatowska-Prokopczuk, E., Hauser, G.J., and Doods, H.N., 1996, Stress-induced mesenteric vasoconstriction in rats is mediated by neuropeptide Y Yl receptors.Am. J. Physiol.270: H796–H800.PubMedGoogle Scholar
  206. Zukowska-Grojec, Z., Karwatowska-Prokopczuk, E., Rose, W., Rone, J., Movafagh, S., Ji, H., Yeh, Y., Chen, W.T., Kleinman, H.K., Grouzmann, E., and Grant, D.S., 1998, Neuropeptide Y: a novel angiogenic factor from the sympathetic nerves and endothelium.Circ. Res.S3: 187–195.Google Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Ingrid de Meester
    • 1
  • Christine Durinx
    • 1
  • Paul Proost
    • 2
  • Simon Scharpé
    • 1
  • Anne-Marie Lambier
    • 1
  1. 1.Laboratory of Clinical BiochemistryUniversity of AntwerpAntwerpBelgium
  2. 2.Laboratory of Molecular Immunology, Rega Institute for Medical ResearchUniversity of LeuvenLeuvenBelgium

Personalised recommendations